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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microvacuolar steatosis in periportal regions of the liver lobule was produced by injection of fasted rats with a single dose of valproate (500 mg/kg, subcutaneously). In livers perfused in the absence of exogenous fatty acids, ketone body (acetoacetate + beta-hydroxybutyrate) production was decreased by valproate (500 microM) maximally by 67%. Concomitantly, NADH fluorescence detected from the liver surface declined about 30% with a time course similar to that of the inhibition of ketogenesis. Valproate had little effect on oxygen uptake but caused an elevation of the steady state level of catalase-H2O2 corresponding to an increase in H2O2 production of about 6 mumol/g/hr. In addition, valproate decreased the rate of oxidized glutathione release into bile by 45% but had little effect on bile flow. In the presence of oleate (250 microM), valproate inhibited ketone body production by 46% and decreased NADH fluorescence by 39%. Rates of ketogenesis in periportal and pericentral regions of the liver lobule were calculated from changes in NADH fluorescence detected with micro-light guides during infusion of valproate in the presence and absence of fatty acids. In the absence of valproate, endogenous ketogenesis was about 35 mumol/g/hr in both regions of the liver lobule. In the presence of oleate, however, rates were significantly higher in pericentral regions (89 +/- 2 mumol/g/hr) than in periportal areas (71 +/- 3 mumol/g/hr). In the presence of added oleate, valproate decreased rates of ketogenesis to 34 +/- 4 mumol/g/hr in periportal regions and 51 +/- 3 mumol/g/hr in pericentral areas. We conclude, therefore, that fat accumulates in periportal areas because valproate depresses ketogenesis to a greater extent in hepatocytes localized around the portal triad.
Mol Pharmacol 1986 Dec
PMID:Mechanism of zone-specific hepatic steatosis caused by valproate: inhibition of ketogenesis in periportal regions of the liver lobule. 309 99

In an isolated, normothermic rat heart model (Langendorff, 37 degrees C), dimethylthiourea (DMTU) infusion only during reperfusion reduced both injury and measurable hydrogen peroxide (H2O2) concentrations after global ischemia. Cardiac function was assessed by measurement of ventricular developed pressure (DP). H2O2 was assessed using H2O2 dependent aminotriazole inactivation of myocardial catalase. Depletion of xanthine oxidase by two methods (tungsten or allopurinol inhibition) also improved recovery of function and H2O2 production. The results indicate that XO derived H2O2 contributes to myocardial reperfusion injury.
Mol Cell Biochem 1988 Dec
PMID:Hydrogen peroxide mediates reperfusion injury in the isolated rat heart. 314 10

In bacterial cells near-ultraviolet radiation (NUV) generates H2O2 which can be decomposed by endogenous catalase to H2O and O2. To assess the roles of H2O2 and catalase in NUV lethality, we manipulated the amount of intracellular catalase (a) by the use of mutant and plasmid strains with altered endogenous catalase, (b) physiologically, by the addition of glucose, and (c) by induction of catalase synthesis with oxidizing agents. Not only was there no direct correlation between NUV-resistance and catalase activity, but in some cases the correlation was inverse. Also, while there was correlation between NUV and H2O2 sensitivity for most strains tested, there were a number of exceptions which indicates that the modes of killing were different for the two agents.
Mol Gen Genet 1987 Apr
PMID:Catalase has only a minor role in protection against near-ultraviolet radiation damage in bacteria. 329 3

Despite decades of study of the effect of near-ultraviolet radiation (NUV) on bacterial cells, insights into mechanisms of deleterious alterations and subsequent recovery are just now emerging. These insights are based on observations that 1) damage by NUV may be caused by a reactive oxygen molecule, since H2O2 may be a photoproduct of NUV; 2) some, but not all, of the effects of NUV and H2O2 are interchangeable; 3) there is an inducible regulon (oxyR) that responds to oxidative stress and is involved in protection against NUV; 4) a number of NUV-sensitive mutants are defective either in the capacity to detoxify reactive oxygen molecules or to repair DNA damage caused by NUV; and 5) recovery from NUV damage may not directly involve induction of the SOS response. Since several distinctly different photoreceptors and targets are involved, it is unknown whether NUV lethality and mutagenesis result from an accumulation of damages or whether there is a particularly critical photoeffect. To fully understand the mechanisms involved, it is important to identify the chromophore(s) of NUV, the mechanism of toxic oxygen species generation, the role of the oxidative defense regulon (oxyR), the specific lesions in the DNA, and the enzymatic events of subsequent repair.
Environ Mol Mutagen 1987
PMID:Mutagenic and lethal effects of near-ultraviolet radiation (290-400 nm) on bacteria and phage. 331 55

Oxidative damage produced by oxygen free radicals has been investigated in various mammalian cells in culture. Incubation of these cells with redox cycling quinones resulted in a stimulation of superoxide anion and hydrogen peroxide formation. Further metabolism of H2O2 by glutathione peroxidase caused oxidation and depletion of cellular glutathione followed by oxidation of protein sulfhydryl groups and cytotoxicity. Several targets susceptible to oxidative modification have been identified, including the mitochondrial, endoplasmic reticular, and plasma membrane Ca2+-translocases. As result, a marked and sustained increase in cytosolic free Ca2+ concentration occurred, followed by the activation of some catabolic Ca2+-dependent processes, namely phospholipases, proteases, and endonucleases. In addition, an impairment of the transmembranal signal-transducing system(s) was found. Recent investigations demonstrated that several modifications occur also in the cytoskeleton of oxidative stress-challenged cells. They mainly consist of oxidative actin cross-linking and dissociation of the cytoskeleton from the plasma membrane. All these alterations appear to contribute to the multifactorial process underlying the irreversible cell injury caused by oxidative stress.
Mol Toxicol
PMID:Oxidative stress injury studied in isolated intact cells. 333 5

Addition of hemoglobin, methemoglobin, hemin or hematin in the assay mixture of rat liver 3-hydroxy-3-methylglutaryl CoA (HMGCoA) reductase inhibited the activity of the enzyme. The inhibition by hemin was rapid, without any apparent dependence on time of preincubation. At 20 microM hemin, a maximum of about 50% inhibition was obtained in the case of the microsomal enzyme while the solubilized enzyme showed almost 80% inhibition. Dithiothreitol at high concentrations or either of the two substrates of the enzyme (HMGCoA and NADPH) could afford partial protection when added before hemin. The Km for both the substrates increased in the presence of hemin. The inhibition by hemin appeared to be irreversible, the presence of KCN or NaN3 being the only means of preventing the inhibition. Molecular oxygen was required for the inhibition. Oxygen radicals and H2O2, however, did not seem to be involved. This offered a clue that an oxidation reaction of the reductase protein may be the likely mechanism of its inactivation. The enzyme protein did not, however, get degraded under the conditions of inhibition.
Mol Cell Biochem 1987 Oct
PMID:Hemin-mediated oxidative inactivation of 3-hydroxy-3-methylglutaryl CoA reductase. 343 83

Hemin catalyses the oxidation of dithiothreitol. One mole of oxygen is consumed for every 2 moles of dithiothreitol oxidized and the product is shown by spectral studies to be the intramolecular disulphide. The reaction shows a specificity for dithiol and for free heme moieties. Hemin molecules exhibit cooperativity in oxygen reduction. Oxygen radicals do not seem to be involved. H2O2 is not required for this oxidation of dithiothreitol and does not appear to be an intermediate in the reduction of O2 to H2O. However, an independent minor reaction involving a 2-electron transfer with the formation of H2O2 also occurs. These studies on the hemin-catalyzed oxidation of dithiothreitol provide a chemical model for a direct 4-electron reduction of O2 to H2O.
Mol Cell Biochem 1987 Oct
PMID:Hemin-mediated oxidation of dithiothreitol reduces oxygen to H2O. 343 84

We used isolated, buffer-perfused rabbit hearts to evaluate whether global, normothermic ischemia altered mitochondrial hydrogen peroxide (H2O2) generation and mitochondrial activities of the major enzymes responsible for degrading H2O2 and superoxide anion (O2-.): glutathione peroxidase (GPD) and superoxide dismutase (SOD), respectively. This preparation lacks exogenous neutrophils and endogenous xanthine oxidase, which are other potential sources of oxygen metabolites. Ischemia depressed mitochondrial oxidative phosphorylation parameters, State 4 succinate-supported H2O2 generation rates, and the relative flux of State 4 oxygen consumption that was diverted to H2O2 formation. The production of H2O2 was not abolished. Ischemia and reperfusion significantly reduced the activities of SOD (by 43%) and GPD (by 39%) in the mitochondrial fraction. Cytosolic GPD activity was also depressed. The results suggest that the myocardial cell's ability to enzymatically degrade H2O2 and O2-. is compromised, particularly in the mitochondrion. Although mitochondrial H2O2 production is decreased, the mitochondria may persist as a source of this oxygen metabolite following ischemia. Collectively, the data may help explain why mitochondria are vulnerable targets of free radical-mediated damage due to ischemia.
J Mol Cell Cardiol 1987 Dec
PMID:Mitochondrial hydrogen peroxide generation and activities of glutathione peroxidase and superoxide dismutase following global ischemia. 344 86

Peroxidases are known to be involved in the intracellular metabolism of H2O2 coupled with various physiological functions. Apart from the thyroid gland, the enzyme has been isolated from various extrathyroidal sources of which salivary gland is one of the richest sources of the enzyme. The enzyme from bovine and goat submaxillary gland has been extensively studied in terms of their molecular, spectral, kinetic, catalytic and immunological properties and compared with the lactoperoxidase which is similar to the salivary peroxidase. The modulation of the salivary peroxidase by various factors and the probable mechanism of the modulation has been described. The enzyme has also been compared with the thyroid peroxidase as regards their physicochemical properties as well as on the immunological and functional aspects. The similarities and dissimilarities have been incorporated. The possible function of the enzyme in iodine metabolism and in bactericidal action has been discussed.
Mol Cell Biochem 1986 Apr
PMID:Salivary peroxidases. 352 Feb 91

A wide variety of agents are shown to mimic insulin action and inhibit rates of intracellular protein degradation in H35 hepatoma cells. For oxidizing agents such as NaNO2, H2O2 and oxidized glutathione, inhibition of protein breakdown is reversed by adding catalase. Phenylhydrazine behaves like an oxidant and mimics insulin action in a manner potentiated by superoxide dismutase and reversed by catalase. Similarly the effect of insulin itself is increased by superoxide dismutase and reduced by catalase. Sulfhydryl reagents also mimic insulin action: inhibition of protein breakdown is seen following addition of 2-mercaptoethanol or a brief pre-treatment with N-ethylmaleimide or iodoacetate. Mild pre-treatment with trypsin also inhibits subsequent rates of protein breakdown. A model is proposed suggesting that these insulinomimetic actions involve a common mechanism which links the generation of active oxygen species through the redox potential of the cell to the activation of a proteinase.
Mol Cell Biochem 1986 Aug
PMID:The effect of insulinomimetic agents on protein degradation in H35 hepatoma cells. 353 45


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